To address the deficiency in our knowledge of what defines an FGF target gene, we are initiating a project to molecularly define the cis-acting elements that cause FGF targets genes to respond to FGF signals. One arm of this project involves characterizing the elements that regulate the expression of Sprouty2 and Sprouty4, two well characterized FGF target genes that encode proteins that regulate the FGF signaling pathway. We have determined that these Sprouty genes also respond to BMP signaling in our Bmpr mutants that are described in project ZIA BC 010518 (Role of BMP and FGF signaling during limb development). Therefore we are also exploring the idea that the key control elements in Sprouty genes that may be regulated by an interaction between BMP and FGF signaling. Also , this work grows organically out of insights gained from project ZIA BC 010518. In our preliminary studies we have defined sequences derived from Sprouty2 that drive expression in three key regions of embryonic FGF signaling. We will use these elements, as positive controls, define a cell culture system in which to assay FGF responsiveness. Such a system will be used, in our second arm of this project, to screen novel libraries to define regions of FGF responsiveness in the mouse genome. We will always validate any in vitro insights with in vivo experiments, thus providing a powerful approach that should guarantee the significance of our data.